Antagonistic effects of the selective, competitive N-methyl-D-aspartate (NMDA) receptor antagonist, NPC 12626, on kappa opiate-induced analgesia in male deer mice.

The present study examined the effects of the competitive NMDA antagonist, NPC 12626, on the analgesic effects of the specific kappa opiate receptor agonist, U69,593, in male deer mice. Intraperitoneal (i.p.) administration of NPC 12626 had no effect on the basal nociceptive sensitivity of reproductive male deer mice, as measured by latency of response to a thermal (50 degrees C) surface. NPC 12626 dose-dependently (0.05-1.0 mg/kg) reduced U69,593-induced analgesia. NPC 12626 at 1.0 mg/kg attenuated U69,593-induced analgesia in a manner comparable to that produced by the specific kappa opiate antagonist, nor-binaltorphimine. In contrast, this dose of NPC 12626 potentiated the analgesia produced by the predominantly mu agonist morphine (1.0 mg/kg). The non-competitive NMDA antagonist, MK-801, which has been previously indicated to affect kappa opiate analgesia, significantly reduced at 1.0 mg/kg, but did not block, the analgesia produced by U69,593 and in contrast to NPC 12626, slightly reduced morphine-induced analgesia. These findings suggest that the NMDA antagonist, NPC 12626, may, either directly or indirectly, have effects on kappa opiate receptor mediated mechanisms.